We propose to synthesize members of four classes of biologically important natural products: the macrocyclic rifamycins, streptovaricins, and polyene macrolides, as well as related compounds such as tirandamycin. These materials exhibit significant antitumor, antibiotic, and antifungal properties, and provide a continuing challenge to the synthetic chemist. In the preceding grant period, we developed a number of versatile methods for acyclic stereocontrol with relative asymmetric induction, based on the functionalization of olefins via cyclic intermediates. We intend to employ these methods in the syntheses proposed, as well as to develop a number of new ones.